Journal Article

DA-DRD5 signaling controls colitis by regulating colonic M1/M2 macrophage polarization

Wu, Yuqing, Wang, Bingwei, Lin, Lin, Jiang, Yuying, Li, Xiaoxi, Yang, Shuo, Liu, Lu

2021

Overview

The decrease of neurotransmitter dopamine (DA) levels in the intestine is closely related to the development of inflammatory bowel disease (IBD). However, the functional relevance and underlying mechanistic basis of the effects of DA signaling on IBD remains unclear. Here, we observed that the DRD5 receptor is highly expressed in colonic macrophages, and the deficiency of DA-DRD5 signaling exacerbated experimental colitis. Moreover, DA-DRD5 signaling can inhibit M1 by negatively regulating NF-κB signaling but promote M2 macrophage polarization through activation of the CREB pathway, respectively. The deficiency of DRD5 signaling increased colonic M1 macrophages but reduced M2 cells during colitis. Additionally, the administration of a D1-like agonist that has a higher affinity to DRD5 can attenuate the colitogenic phenotype of mice. Collectively, these findings provide the first demonstration of DA-DRD5 signaling in colonic macrophages controlling the development of colitis by regulating M1/M2 macrophage polarization.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 13/1 / 13/21 / 13/31 / 13/95 / 38/22 / 38/23 / 38/39 / 38/77 / 38/90 / 38/91 / 631/250/2504/342 / 631/250/256 / 82/51 / 82/80 / 96/34 / Animals / Antibodies / Biochemistry / Biomedical and Life Sciences / Cell activation / Cell Biology / Cell Culture / Colitis / Colitis - metabolism / Cyclic AMP response element-binding protein / Dopamine D1 receptors / Dopamine D5 receptors / Immunology / Inflammation - metabolism / Inflammatory bowel disease / Inflammatory bowel diseases / Intestine / Life Sciences / Macrophages / Macrophages - metabolism / Male / Mice / NF-κB protein / Phenotypes / Polarization / Receptors, Dopamine D5 - metabolism